Zeitschriftenaufsatz
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2025
Anti-Cancer Potential of a new Derivative of Caffeic Acid Phenethyl Ester targeting the Centrosome
Autor:in
Giordano, Catello; Kendler, Jonatan; Sexl, Maximilian; Kollman, Sebastian; Varenicja, Maxim; Szabo, Boglarka; Timelthaler, Gerald; Kirchhofer, Dominik; Holloczki, Oldamur; Turner, Suzanne; Moriggl, Richard; Kenner, Lukas; Touaibia, Mohamed; Merkel, Olaf
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Journal
Abstrakt
Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma affecting children and young adults. About 30% of patients develop therapy resistance therefore new precision medicine drugs are highly warranted. Multiple rounds of structure-activity optimization of Caffeic Acid Phenethyl Ester have resulted in CM14. CM14 causes upregulation of genes involved in oxidative stress response and downregulation of DNA replication genes leading to G2/M arrest and subsequent apoptosis induction. In accordance with this, an unbiased proteomics approach, confocal microscopy and molecular modeling showed that TUBGCP2, member of the centrosomal gamma-TuRC complex, is a direct interaction partner of CM14. CM14 overcomes ALK inhibitor resistance in ALCL and is also active in T-cell Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia. Interestingly, CM14 also induced cell death in docetaxel-resistant prostate cancer cells thus suggesting an unexpected role in solid cancers. Thus, we synthesized and thoroughly characterized a novel TUBGCP2 targeting drug that is active in ALCL but has also potential for other malignancies.
Schlagwörter
Humans; Caffeic Acidspharmacologychemistry; Phenylethyl Alcoholanalogs & derivativespharmacologychemistry; Centrosomedrug effectsmetabolism; Antineoplastic Agentspharmacologychemistry; Apoptosisdrug effects; Cell Line, Tumor; Cell Proliferationdrug effects
Dokumententyp
Originalarbeit
CC Lizenz
CCBY
Open Access Type
Gold
ISSN/eISSN
2213-2317 -
10.1016/j.redox.2025.103582
WoS ID
PubMed ID
Repository Phaidra